© 2016 John Wiley & Sons Ltd Background: Acromegaly (ACRO) is associated with elevated cardiovascular risk, although the prevalence of coronary artery disease (CAD) is unclear. Increased epicardial adipose tissue (EAT) and elevated cystatin-C (Cys-C) levels are cardiovascular risk factors, also related to the progression of CAD in several populations. Aims: To measure the severity and extent of CAD in patients with ACRO and to determine whether either EAT or Cys-C reflect higher cardiovascular risk in patients with ACRO than in healthy controls. Subjects and methods: Case–control study, of 35 patients with ACRO (19 males, 17 with active disease) and 35 age-, gender- and body mass index (BMI)-matched healthy controls; mean age was 48·1 ± 8·1 years and mean BMI was 27·6 ± 4·8 kg/m2. Cys-C was measured by an immunoturbidimetric assay. The 10-year risk of developing a coronary event was calculated using the Framingham Risk Score (FRS). EAT index (volume indexed to body surface area), and severity and extent of CAD were measured using a 256-slice multidetector computed tomography scanner (iCT-256 Philips Healthcare, Amsterdam). Results: Coronary artery disease lesions, EAT index and severity/extent of CAD were similar between patients with ACRO and controls. Forty-four per cent of patients with ACRO had mild coronary lesions associated with greater EAT index (ß = 0·022, P = 0·036). Cys-C levels correlated with both EAT index (ρ = 0·386, P = 0·031) and FRS (ρ = 0·477, P = 0·004) in patients with ACRO only, despite similar prevalence of traditional cardiovascular risk factors. In a multiple linear regression model, both Cys-C levels (ß = 0·369, P = 0·007) and EAT index (ß = 0·29, P = 0·025) predicted FRS (R2 = 0·613). Conclusions: In patients with ACRO, both Cys-C and EAT index might be used as noninvasive predictors of cardiovascular risk.